The development and progression of ischemic cerebral edema have been associated with changes in serotonin (5-HT) metabolism. The present study represents a continuous effort to shed more light on the pathomechanisms of ischemic cerebral edema. These investigations centered to ascertain more closely the relationship between the changes of postsynaptic S2-receptors in synaptosomes and the degree of cerebral of edema formation induced by ischemia of different duration. Mongolian gerbils subjected to 5 or 15 min. of bilateral common carotid artery occlusion with and without 1 hr release served as the model for this study. The alteration of 3H-ketanserin (the potent 5-HT antagonist which labels specifically S2-receptor sites) binding sites in synaptosomes was found in association with an increase release of 5-HT and accumulation of water in the brain after 15 min of ischemic insult only. Thus, these findings substantiate the implicated serotoninergic participation in pathogenesis of ischemic brain edema.